Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channels.
A functional kinetic model is developed to describe the activation gating process of the Shaker potassium channel. The modeling in this paper is constrained by measurements described in the preceding two papers, including macroscopic ionic and gating currents and single channel ionic currents. These data were obtained from the normally activating wild-type channel as well as a mutant channel V2, in which the leucine at position 382 has been mutated to a valine. Different classes of models that incorporate Shaker's symmetrical tetrameric structure are systematically examined. Many simple gating models are clearly inadequate, but a model that can account for all of the qualitative features of the data has the channel open after its four subunits undergo three transitions in sequence, and two final transitions that reflect the concerted action of the four subunits. In this model, which we call Scheme 3+2', the channel can also close to several states that are not part of the activation path. Channel opening involves a large total charge movement (10.8 e0), which is distributed among a large number of small steps each with rather small charge movements (between 0.6 and 1.05 e0). The final two transitions are different from earlier steps by having slow backward rates. These steps confer a cooperative mechanism of channel opening at Shaker's activation voltages. In the context of Scheme 3+2', significant effects of the V2 mutation are limited to the backward rates of the final two transitions, implying that L382 plays an important role in the conformational stability of the final two states.
Schoppa
N E
NE
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sigworth
F J
FJ
D000818:Animals; D001711:Biotransformation / Q000235:genetics / Q000502:physiology; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000235:genetics* / Q000502:physiology*; D007473:Ion Channels; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008954:Models, Biological; D009154:Mutation / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D014982:Xenopus laevis
D007473:Ion Channels; D015221:Potassium Channels